The present invention relates to a process and an apparatus for the automated manufacture of a gastro-retentive device. An example of such a device is a retard form of the type disclosed in U.S. Pat. No. 4,996,058, which is hereby incorporated herein by reference, although the present invention is not limited to such retard forms, but is applicable to any gastro-retentive device.
The term “retard form,” denotes a dosage form which effects delayed release of at least a portion of the active ingredient in the stomach and to the upper part of the small intestine in comparison to conventional dosage forms, such as customary tablets or capsules. Avoiding an undesirably high initial dose, the release is effected continuously over a relatively long period and controlled at an effective level. The retard form is administered orally and, once in contact with the stomach fluids, expands so as to float on the stomach fluids and/or be retained within the space of the stomach due to its size following inflation, which precludes passage across the pylorus sphincter. In this manner it remains in the stomach to insure continuous controlled release of the physiologically active ingredients.
A retard form is characterized preferably, at least in one form, by the following: (a) at least one component that expands on contact with bodily fluid (e.g., a substance that generates or constitutes a blowing agent), and/or a physiologically active substance, and/or a combination of physiologically active substances, and/or optionally a pharmaceutically acceptable hydrophilic swelling agent and further pharmaceutically acceptable adjuncts, (b) at least one hydrophilic membrane which surrounds component (a) and which is expansible at the site of use and is permeable to body fluid, and (c) a covering which surrounds component (a) and membrane (b) and which disintegrates without delay under the action of bodily fluid at the site of use in the stomach, e.g., a gelatin capsule.
As an example, a retard form of this type suitable for the present invention could take the following form. A component (a) is provided in the form of a tablet surrounded by and sealed within component (b) in the form of a hydrophilic membrane or film, the membrane forming a pouch in which the tablet sits. The tablet and membrane assembly are fitted within component (c) provided in the form of a gelatin capsule.
Taken orally, the retard form moves to the stomach where the gelatin capsule disintegrates to release the tablet membrane assembly. Upon contact with stomach fluid, the tablet generates the blowing agent, for example carbon dioxide gas. The gas causes the membrane surrounding the tablet to inflate, forming a gas-filled “bag.” This gas-filled “bag” is able to float on the stomach fluids and/or is unable to pass through the pylorus sphincter following inflation, and thus is retained in the stomach. During its dwell time in the stomach, any active ingredients present in the tablet are released slowly and/or in a controlled manner into the surrounding body fluid, preferably by diffusion, through the membrane. Since gastric juice is being transported further into the upper part of the small intestine, the active ingredient passes continuously and over a prolonged period into the duodenum and jejunum, where it can be absorbed over an extended period. The retard form ensures continuous release of any active ingredient in conjunction with uniform absorption, or at least that the device will remain in the stomach for the desired time period. Once the gas generating components are used up, and/or the when the “bag” deflates to a certain size, this allows the remainder of the device to pass through the body.
The manufacture of a gastro-retentive device of the general type described above can be complex and includes several challenges. The component(s) (a) or tablet must be sealed within the membrane(s) to form the pouch. Depending on the drug or drugs of choice, the tablet may also contain other excipients which control the release of the drug or drugs from the tablet into the medium of the pouch and subsequently into the gastric fluid of the stomach following diffusion across the pouch. Once formed, the pouch must be folded to fit within the capsule. While such gastro-retentive devices can be produced manually, it is believed that an automated and economical process for producing such forms will help bring the benefits of gastro-retentive devices to the public.